Compositions and treatments for Haemophilus influenzae

Abstract

Immunogenic peptides, fusion polypeptides, and carrier molecules which include the immunogenic peptides, and immunogenic compositions which include these immunogenic peptides, fusion polypeptides, and/or carrier molecules bearing the peptides, and which are able to elicit antibody production against Haemophilus influenzae (Hi), are disclosed. Also disclosed are methods of their use in causing an antibody response against one or more strains of Hi.

What is claimed is: 
     
       1. A peptide composition, comprising a plurality of peptides comprising at least two different amino acid sequences, wherein each of the at least two different amino acid sequences is from an externally exposed loop of an outer membrane protein (OMP) selected from the group consisting of:
 SEQ ID NO: 97, SEQ ID NO: 101, SEQ ID NO: 589, SEQ ID NO: 462, SEQ ID NO: 590, SEQ ID NO: 308, SEQ ID NO: 123, SEQ ID NO: 139, SEQ ID NO: 245, SEQ ID NO: 460, SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO: 153, SEQ ID NO: 321, SEQ ID NO: 325, SEQ ID NO: 145, SEQ ID NO: 350, SEQ ID NO: 268, SEQ ID NO: 341, and SEQ ID NO: 517, 
 wherein each of the peptides induces an antibody response against a Nontypeable  Haemophilus influenzae  (NTHi), each of the peptides is linked together to form a fusion polypeptide, and a peptide at the amino-terminal end of the fusion polypeptide is duplicated at the carboxy terminal end of the fusion polypeptide. 
 
     
     
       2. The peptide composition of  claim 1 , wherein the at least two different amino acid sequences are linked to a carrier molecule to form a carrier molecule composition. 
     
     
       3. The peptide composition of  claim 1 , further defined as being able to induce an antibody response against at least one type b strain of  Haemophilus influenzae.    
     
     
       4. The peptide composition of  claim 1 , further comprising a pharmaceutically acceptable carrier, vehicle, diluent, and/or adjuvant. 
     
     
       5. The peptide composition of  claim 1 , further defined as comprising at least five of said amino acid sequences. 
     
     
       6. The peptide composition of  claim 5 , wherein the at least five amino acid sequences are linked to a carrier molecule to form a carrier molecule composition. 
     
     
       7. The peptide composition of  claim 1 , wherein the at least two different amino acid sequences comprise:
 SEQ ID NO: 328 from an outer membrane (OM) protein assembly factor BamA; and 
 SEQ ID NO: 462 and/or SEQ ID NO: 590 from an outer membrane protein P4 designated Hel. 
 
     
     
       8. The peptide composition of  claim 1 , wherein the at least two different amino acid sequences comprise:
 SEQ ID NO: 328 from an OM protein assembly factor designated BamA; and 
 SEQ ID NO: 145 from a 5′-nucleotidase designated NucA. 
 
     
     
       9. The peptide composition of  claim 1 , wherein the at least two different amino acid sequences comprise:
 SEQ ID NO: 328 from an OM protein assembly factor designated BamA; and 
 SEQ ID NO: 321 and/or SEQ ID NO: 325 from a lipopolysaccharide (LPS) assembly outer membrane (OM) complex LptDE component protein designated 1ptE. 
 
     
     
       10. The peptide composition of  claim 1 , wherein the at least two different amino acid sequences comprise:
 SEQ ID NO: 328 from an OM protein assembly factor designated BamA; and 
 SEQ ID NO: 139 from a lipoprotein designated N1pI. 
 
     
     
       11. A peptide composition, comprising a plurality of peptides comprising at least two different amino acid sequences,
 wherein each of the at least two different amino acid sequences is from an externally exposed loop of an outer membrane protein (OMP) and at least one of the amino acid sequences is SEQ ID NO: 328, and 
 wherein each of the peptides induces an antibody response against a Nontypeable  Haemophilus influenzae  (NTHi), each of the peptides is linked together to form a fusion polypeptide, and a peptide at the amino-terminal end of the fusion polypeptide is duplicated at the carboxy terminal end of the fusion polypeptide. 
 
     
     
       12. The peptide composition of  claim 11 , wherein the peptide composition further comprises peptides having amino acid sequences SEQ ID NO: 462, SEQ ID NO: 590, and SEQ ID NO: 145. 
     
     
       13. The peptide composition of  claim 11 , wherein the peptide composition further comprises peptides having amino acid sequences SEQ ID NO: 321 and SEQ ID NO: 139. 
     
     
       14. The peptide composition of  claim 11 , wherein the peptide composition further comprises peptides having amino acid sequences SEQ ID NO: 462, SEQ ID NO: 590, SEQ ID NO: 145, SEQ ID NO: 321, and SEQ ID NO: 139. 
     
     
       15. A method of inducing an immunogenic response in a subject, comprising the step of:
 administering to the subject an amount of a peptide composition which is effective in stimulating an immunogenic response against Nontypeable  Haemophilus influenza  (NTHi) in the subject, wherein the peptide composition comprises at least two different amino acid sequences, wherein each the at least two different amino acid sequences is from an externally exposed loop of an outer membrane protein (OMP) selected from the group consisting of: 
 SEQ ID NO: 97, SEQ ID NO: 101, SEQ ID NO: 589, SEQ ID NO: 462, SEQ ID NO: 590, SEQ ID NO: 308, SEQ ID NO: 123, SEQ ID NO: 139, SEQ ID NO: 245, SEQ ID NO: 460, SEQ ID NO: 328, SEQ ID NO: 329, SEQ ID NO: 153, SEQ ID NO: 321, SEQ ID NO: 325, SEQ ID NO: 145, SEQ ID NO: 350, SEQ ID NO: 268, SEQ ID NO: 341, and SEQ ID NO: 517, and 
 wherein each of the at least two different amino acid sequences is able to induce an antibody response against NTHi, each of the peptides is linked together to form a fusion polypeptide, and a peptide at the amino-terminal end of the fusion polypeptide is duplicated at the carboxy terminal end of the fusion polypeptide. 
 
     
     
       16. The method of  claim 15 , wherein the peptide composition is also effective in inducing an antibody response against at least one type b strain of  Haemophilus influenzae.    
     
     
       17. The method of  claim 15 , wherein the peptide composition comprises at least five of said amino acid sequences. 
     
     
       18. The method of  claim 17 , wherein the at least five amino acid sequences of the peptide composition are linked to a carrier molecule to form a carrier molecule composition.